Several forms of delayed-onset, lymphocyte-mediated hypersensitivity in animals and man are characterized by extensive infiltrations of basophilic leukocytes; these include "Jones-Mote" hypersensitivity to protein antigens as well as biologically more significant expressions of cellular immunity such as viral and contact allergy and allograft and tumor rejection. We designated these basophil-rich reactions cutaneous basophil hypersensitivity (CBH) to distinguish them from classic delayed hypersensitivity (DH). In addition to basophils, CBH reactions differ from those of DH in that they lack substantial fibrin deposition and are not indurated. One goal of this research is to define the macromolecules of basophilic leukocyte granules and to elucidate their functions, particularly in the reactions of CBH. This investigation has been facilitated by our recent development of reliable methods for the isolation of highly purified guinea pig basophils and their cytoplasmic granules. Our studies will concentrate on solubilizing, purifying, and characterizing the esterases/proteases and the acid mucopolysaccharides (proteoglycans) we have found in basophil granules. Attention will also be devoted to the plasminogen activator we have localized to a basophil membrane fraction. Attempts will be made to relate these molecules to basophil function in CBH. A second goal is to elucidate the pathogenesis of CBH. We will seek to determine whether antibodies have a necessary role in the pathogenesis of these reactions. We will also attempt to define the mechanisms by which the clotting system is activated in cell-mediated hypersensitivity and to account for the much greater deposition of fibrin regularly present in DH, as compared with CBH.